Water-Swellable Copolymers and Articles and Coatings Made Therefrom

ABSTRACT

The present disclosure relates to compositions comprising a copolymer that includes a first monomer and a second monomer that is different from the first monomer, wherein both the first and second monomer are selected from the group consisting of 3-sulfopropyl acrylate potassium salt, sodium acrylate, N-(tris(hydroxyl methyl)methyl)acrylamide, and 2-acrylamide-2-methyl-1-propane sulfonic acid. The present disclosure further relates to methods for preparing the copolymer compositions and shaped articles comprising the copolymers.

CROSS-REFERENCE TO RELATED APPLICATION

The present application claims the benefit of and priority to U.S.Provisional Application Ser. No. 60/602,689, filed on Aug. 19, 2004, theentire disclosure of which is incorporated herein by reference.

TECHNICAL FIELD

This disclosure relates, generally, to the medical arts. Moreparticularly, it relates to devices and compositions for sealingopenings in tissue.

BACKGROUND OF RELATED ART

Openings may be formed in tissue by numerous means. For example, anopening in tissue may be created intentionally during a medicalprocedure (e.g., via use of a needle, trocar, scalpel, etc.) or may beaccidentally created through trauma. In general, the existence of anopening in tissue over time is undesirable and requires closure.

Many techniques have been developed for the surgical closing ofopenings. Sutures were invented long ago, for example. Typically, if asuture is used to close an opening in tissue, a smaller openingtypically remains as a result of the fact that the passage of the needlethrough tissue creates an opening having the same diameter as the needlewhich opening is not fully occupied by the suture which is typically ofa smaller diameter than the needle. Thus, leaking at the site ofsuturing may arise in some applications.

Another technique for closing openings in tissue includes the use ofstaples. As those skilled in the art will appreciate, the application ofstaples may result in smaller openings being formed at the site ofstaple application as the legs of the staples pass through tissue.

It would be advantageous to provide means for easily and reliablyclosing openings in tissue, without leaving additional openings, howeversmall.

SUMMARY

Compositions in accordance with this disclosure are water-swellable andcan thus be used to close openings in tissue. The compositions include acopolymer containing repeating units of two or more monomers selectedfrom the group consisting of 3-sulfopropyl acrylate potassium salt(“KSPA”), sodium acrylate (“NaA”), N-(tris(hydroxylmethyl)methyl)acrylamide (“tris acryl”), and2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS). The compositionscan formed into a desired shape or may be used to coat at least aportion of a medical device, such as a hernia mesh, suture or surgicalstaple. After being dried, the copolymer will swell upon contact withmoisture, such as blood or other bodily fluid.

BRIEF DESCRIPTION OF DRAWINGS

For a fuller understanding of the subject matter described herein,reference should be made to the following detailed description, taken inconnection with the accompanying diagrammatic drawings, in which:

FIG. 1 shows a suture having a coating of a water-swellable compositionin accordance with this disclosure; and

FIG. 2 shows a staple having a coating of a water-swellable compositionin accordance with this disclosure.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Water-swellable compositions are described herein that are useful inclosing openings in tissue. The compositions include a copolymercontaining repeating units of two or more monomers selected from thegroup consisting of 3-sulfopropyl acrylate potassium salt (“KSPA”),sodium acrylate (“NaA”), N-(tris(hydroxyl methyl)methyl)acrylamide(“tris acryl”), and 2-acrylamido-2-methyl-1-propane sulfonic acid(AMPS). Thus, the copolymer includes a first monomer and a secondmonomer that is different from the first monomer, wherein both the firstand second monomer are selected from the group consisting of3-sulfopropyl acrylate potassium salt (“KSPA”), sodium acrylate (“NaA”),N-(tris(hydroxyl methyl)methyl)acrylamide (“tris acryl”), and2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS). The first monomercan be from 5 to 95 percent of the total monomer used to form thecopolymer and the second monomer can be from 95 to 5 percent of thetotal monomer used to form the copolymer. In particularly usefulembodiments, the first monomer can be from 25 to 75 percent of the totalmonomer used to form the copolymer and the second monomer can be from 75to 25 percent of the total monomer used to form the copolymer. Anotherembodiment includes homopolymers derived from KSPA, NaA, trisacryl andAMPS. It is further contemplated that the composition may includehydrophilicity modifying monomers copolymerizable therewith. Suitablehydrophilicity modifying monomers include but are not limited tomethylmethacrylate, butylacrylate, cyclohexylacrylate, styrene, styrenesulphonic acid, etc.

The copolymer may be crosslinked. A suitable crosslinker, if present,is, for example, a low molecular weight di- or polyvinylic crosslinkingagent such as ethylenglycol diacrylate or dimethacrylate, di-, tri- ortetraethylen-glycol diacrylate or dimethacrylate, allyl(meth)acrylate, aC₂-C₈-alkylene diacrylate or dimethacrylate, divinyl ether, divinylsulfone, di- and trivinylbenzene, trimethylolpropane triacrylate ortrimethacrylate, pentaerythritol tetraacrylate or tetramethacrylate,bisphenol A diacrylate or dimethacrylate, methylene bisacrylamide or-bismethacrylamide, ethylene bisacrylamide or ethylenebismethacrylamide, triallyl phthalate or diallyl phthalate. The averageweight average molecular weight of the crosslinker is, for example, upto 1000, preferably up to 750 and most preferably up to 500. Aparticularly useful crosslinking agent is N,N′ methylenebisacrylamide(“MBAA”). When used, a crosslinking agent may be used in amounts from0.1 to 20 percent by weight of the copolymer, more preferably from 0.1to 10 percent by weight of the copolymer.

The copolymer may be formed using any technique within the purview ofone skilled in the art. Suitable polymerization conditions will beapparent to those skilled in the art, given the particular startingmaterials chosen. In certain embodiments, the copolymer is prepared withthe use of polymerization initiator. Suitable polymerization initiatorsare typically those that are initiating a radical polymerization ofethylenically unsaturated compounds. The radical polymerization may beinduced thermally or by radiation (e.g., UV, visible, IR, γ, E-beam andthe like). In particularly useful embodiments, UV or visible light isused to induce polymerization. Redox initiation may also be used.

Suitable thermal polymerization initiators are known to the skilledartisan and include for example peroxides, hydroperoxides, azobis(alkyl-or cycloalkylnitriles), persulfates, percarbonates or mixtures thereof.Examples are benzoylperoxide, tert-butyl peroxide,tert-butylperoxybenzoate, di-tert-butyl-diperoxyphthalate, tert-butylhydroperoxide, 2,2′-azobisisobutyronitrile,1,1′-azobis(cyclohexanecarbonitrile), 4,4′-azobis(4-cyanovaleric acid)and the like.

Initiators for the radiation-induced polymerization, so-calledphotoinitiators, fall into two groups based on the photochemicalprocesses that lead to the production of radicals. These two groups areα-cleavage photoinitiators and hydrogen abstraction photoinitiators.Examples of α-cleavage initiators include benzoin ethers, hydroxy alkylphenyl ketones, dialkoxy acetophenones, methyl thiophenyl morpholinoketones, phosphine oxide derivatives, morpholino phenyl amino ketonesand benzoyl cyclohexanol. Examples of H-abstraction initiators includebenzophenones, thioxanthones, benzyls, camphorquinones andketocoumarins.

Water soluble photoinitiators are particularly useful in thisapplication. These are typically prepared by introducing watersolubilizing groups onto the backbone of the initiator such that they donot significantly alter the activity of the initiator. These groupsinclude quaternary ammonium salts, sulfonate groups, thiosulfate groups,carboxylic acid groups or hydrophilic chains. Some useful water solubleinitiators are based on benzophenones, thioxanthones, benzyls, hydroxylalkyl ketones, benzoyl methyl thiosulfate and phenyl trimethyl benzoylphosphinates. See generally, J. P. Fouassier, PhotoinitiatorPolymerization and Photocuring: Fundamentals and Applications,Hanson/Gardner Publications, Inc., 1995. Useful photoinitiators includefor example benzophenones substituted with an ionic moiety, ahydrophilic moiety or both such as 4-trimethylaminomethyl benzophenonehydrochloride or benzophenone sodium 4-methanesulfonate; benzoin C₁-C₄alkyl ether such as benzoin methyl ether; thioxanthones substituted withan ionic moiety, a hydrophilic moiety or both such as3-(2-hydroxy-3-trimethylaminopropoxy)thioxanthone hydrochloride,3-(3-trimethylaminopropoxy)thioxanthone hydrochloride, thioxanthone3-(2-ethoxysulfonic acid) sodium salt or thioxanthone3-(3-propoxysulfonic acid) sodium salt; or phenyl ketones such as1-hydroxycyclohexylphenyl ketone, (2-hydroxy-2-propyl)(4-diethyleneglycol phenyl)ketone,(2-hydroxy-2-propyl)(phenyl-4-butanecarboxylate)ketone; or commercialproducts such as those available under the tradenames Darocure® orIrgacure®. Using such initiators, copolymers may be polymerized in situby long wavelength ultraviolet light or by light of about 514 nm, forexample. It is known in the art of photopolymerization to use awavelength of light which is appropriate for the activation of aparticular initiator. Light sources of particular wavelengths or bandsare well-known and are commercially available from a variety of sources.

The polymerization initiator can be present in an amount of, forexample, 0.05 to about 5% by weight, based on the entire amount ofmonomer used. A particularly useful photoinitiator is2-hydroxy-1-(4-(2-hydroxyethoxy)-2-methyl-1-propanone (“HEMP”) availablefrom Ciba Specialty Chemicals under the tradename IRGACURE® 2959. Insuch embodiments, an aqueous solution containing the monomers (andoptionally a crosslinking agent) and the photoinitiator is prepared. Thesolution is then exposed to a suitable radiation source, such as a UVlamp, to effectuate polymerization.

Prior to exposure to a radiation source, the solution may be poured ontoa surface so that upon polymerization a sheet is formed. Alternatively,the solution may be poured into a mold to achieve any desired shape uponpolymerization.

In another embodiment, the solution is coated onto at least a portion ofthe surface of a medical device prior to polymerization. Medical devicesonto which the present compositions may be applied include but are notnecessarily limited to: orthopedic pins, clamps, screws and plates;clips; staples; hooks; plugs; buttons; snaps; screws; anchors;anastomosis rings; prosthetic devices; bone substitutes such as mandibleprostheses; needles; non-permanent intrauterine devices such asspermicides; drug delivery devices; temporary draining or testing tubesor capillaries; surgical instruments; vascular and ocular implants orsupports; vertebral discs; fibrillar products, knitted or woven, andincluding velours, such as burn dressings; hernia patches; absorbentpaper or swabs; medicated dressings; facial substitutes; gauze, fabric,sheet, felt, foam or film or gel or particles or sponge for hemostasis,as, e.g., of the liver or other internal organs; gauze bandages; anddental packs. Other products include flake or powder for burns orabrasions; foam as a resorbable prosthesis; wire substitutes infixations; and film sprays for prosthetic devices. The presentcompositions may be used alone or in combination with other materials toproduce products including those listed hereinabove, as well ascomposite products such as reinforced bone pins, needles, arterialgrafts or substitutes and the like.

Optionally, therapeutically beneficial compounds may be incorporatedinto the present compositions, and, after application or implantation ofthe article or coated device, released therefrom. Thebiologically-active agent may be soluble in the polymer solution to forma homogeneous mixture, or insoluble in the polymer solution to form asuspension or dispersion. Over time, the biologically-active agent isreleased from the article or coated device into the adjacent tissuefluids, preferably at a controlled rate. The release of thebiologically-active agent from the present composition may be varied,for example, by the solubility of the biologically-active agent in anaqueous medium, the distribution of the agent within the composition,ion exchange, pH of the medium, the size, shape, porosity, solubilityand biodegradability of the article or coating, and the like.

The term “therapeutically beneficial compound” encompasses therapeuticagents, such as drugs, and also genetic materials and biologicalmaterials. A variety of therapeutically beneficial compounds may beincluded, including passively-functioning materials such as hyaluronicacid, as well as active agents such as growth hormones. All of thecommon chemical classes of such agents are included: proteins (includingenzymes, growth factors, hormones and antibodies), peptides, organicsynthetic molecules, inorganic-compounds, natural extracts, nucleicacids (including genes, telomerase inhibitor genes, antisensenucleotides, ribozymes and triplex forming agents), lipids and steroids,carbohydrates (including heparin), glycoproteins, polymeric drugs, e.g.polysalicilic acid, prodrugs, and combinations thereof. The agents to beincorporated can have a variety of biological activities, such asvasoactive agents, neuroactive agents, hormones, anticoagulants,immunomodulating agents, cytotoxic agents, antibiotics, antivirals, ormay have specific binding properties such as antisense nucleic acids,antigens, antibodies, antibody fragments or a receptor. Proteinsincluding antibodies or antigens can also be delivered. Proteins aredefined as consisting of 100 amino acid residues or more; peptides areless than 100 amino acid residues. Unless otherwise stated, the termprotein refers to both proteins and peptides. Examples include insulinand other hormones.

Specific materials include antibiotics, antivirals, antiinflammatories,both steroidal and non-steroidal, antineoplastics, anti-spasmodicsincluding channel blockers, modulators of cell-extracellular matrixinteractions including cell growth inhibitors and anti-adhesionmolecules, enzymes and enzyme inhibitors, anticoagulants and/orantithrombotic agents, growth factors, DNA, RNA, inhibitors of DNA, RNAor protein synthesis, compounds modulating cell migration, proliferationand/or growth, vasodilating agents, and other drugs commonly used forthe treatment of injury to tissue. Specific examples of these compoundsinclude angiotensin converting enzyme inhibitors, prostacyclin, heparin,salicylates, nitrates, calcium channel blocking drugs, streptokinase,urokinase, tissue plasminogen activator (TPA) and anisoylatedplasminogen activator (TPA) and anisoylated plasminogen-streptokinaseactivator complex (APSAC), colchicine and alkylating agents, andaptomers. Specific examples of modulators of cell interactions includeinterleukins, platelet derived growth factor, acidic and basicfibroblast growth factor (FGF) transformation growth factor β (TGF β)epidermal growth factor (EGF), insulin-like growth factor, andantibodies thereto. Specific examples of nucleic acids include genes andcDNAs encoding proteins, expression vectors, antisense and otheroligonucleotides such as ribozymes which can be used to regulate orprevent gene expression. Specific examples of other bioactive agentsinclude modified extracellular matrix components or their receptors, andlipid and cholesterol sequestrants. Examples of proteins further includecytokines such as interferons and interleukins, poetins, andcolony-stimulating factors. Carbohydrates include sialylatedcarbohydrate ligand (sialyl-Lewis X), a structure found on neutrophilcell-surface glycoproteins and glycolipids which has been shown to bindto receptors for selectins to inhibit inflammation. A “Deliverablegrowth factor equivalent” (abbreviated DGFE), a growth factor for a cellor tissue, may be used, which is broadly construed as including growthfactors, cytokines, interferons, interleukins, proteins,colony-stimulating factors, gibberellins, auxins, and vitamins; furtherincluding peptide fragments or other active fragments of the above; andfurther including vectors, i.e., nucleic acid constructs capable ofsynthesizing such factors in the target cells, whether by transformationor transient expression; and further including effectors which stimulateor depress the synthesis of such factors in the tissue, includingnatural signal molecules, antisense and triplex nucleic acids, and thelike. Exemplary DGFE's are vascular endothelial growth factor (VEGF),endothelial cell growth factor (ECGF), basic fibroblast growth factor(bFGF), bone morphogenetic protein (BMP), and platelet derived growthfactor (PDGF), and DNA's encoding for them. Exemplary clot dissolvingagents are tissue plasminogen activator, streptokinase, urokinase andheparin. Drugs having antioxidant activity (i.e., destroying orpreventing formation of active oxygen) may be used, which are useful,for example, in the prevention of adhesions. Examples include superoxidedismutase, or other protein drugs include catalases, peroxidases andgeneral oxidases or oxidative enzymes such as cytochrome P450,glutathione peroxidase, and other native or denatured hemoproteins;anti-inflammatory agents such as glucocorticoids, betamethasone,dexamethasone, prednisolone, corticosterone, budesonide, estrogen,sulfasalazine, and mesalamine;antineoplastic/antiproliferative/anti-meiotic agents such as paclitaxel,5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones,methotrexate, azathioprine, adriamycin and mutamycin; endostatin,angiostatin and thymidine kinase inhibitors, taxol and its analogs orderivatives; anesthetic agents such as lidocaine, bupivacaine, andropivacaine; anti-coagulants such as D-Phe-Pro-Arg chloromethyl keton,an RGD peptide-containing compound, heparin, antithrombin compounds,platelet receptor antagonists, anti-thrombin antibodies, anti-plateletreceptor antibodies, aspirin (aspirin is also classified as ananalgesic, antipyretic and anti-inflammatory drug), dipyridamole,protamine, hirudin, prostaglandin inhibitors, platelet inhibitors andtick antiplatelet peptides; vasodilating agents; and agents whichinterfere with endogenous vasoactive mechanisms; anti-oxidants, such asprobucol; antibiotic agents, such as penicillin, cefoxitin, oxacillin,tobramycin; angiogenic substances, such as acidic and basic fibroblastgrowth factors, estrogen including estradiol (E2), estriol (E3) and17-Beta Estradiol; and drugs for heart failure, such as digoxin,beta-blockers, angiotensin-converting enzyme (ACE) inhibitors includingcaptopril and enalopril. Other therapeutically beneficial compounds areknown in the art, as described in Pharmaceutical Sciences, by Remington,14th Ed., Mack Publishing Co. (1979); The Drug The Nurse. The Patient,Including Current Drug Handbook, by Falconer et al., Saunder Company(1974-76); and Medicinal Chemistry, 3rd Ed., Vol. 1 and 2, by Burger,Wiley-Interscience Co.

The compositions of this disclosure may also optionally include acontrasting agent to facilitate detection of the article or coatedmedical device by imaging means such as magnetic resonance imaging,ultrasound, Doppler, and roentgenological means including x-ray, CTscan, mammography, and fluoroscopy. Alternatively, the composition mayoptionally include a radioactive substance detectable by a radiationdetecting means including a gamma counter and a scintillation counter.

It is contemplated that it may be desirable to include a dye in thepresent compositions in order to increase visibility in the surgicalfield. Dyes known to be suitable for incorporation in medical devicescan be used. Such dyes include but are not limited to carbon black, boneblack, D&C Green No. 6, and D&C Violet No. 2 as described in thehandbook of U.S. Colorants for Food, Drugs and Cosmetics by Daniel M.Marrion (1979).

After the polymerization of the composition, the resulting shapedarticle or coated medical device is preferably dried, packaged inmaterials which are not moisture-permeable, and sterilized before useunder clinical conditions. Drying can be accomplished by vacuum-dryingof the apparatus under conditions well known in the art. After drying,the apparatus can be heat-sealed inside a moisture-proof material (e.g.,foil laminate), and sterilized, for example, by γ-radiation, or othermeans, to sterilize the article or coated medical device. The device canbe stored and shipped thereafter.

Articles or coated medical devices made in accordance with the presentdisclosure can be used in a variety of ways to close an opening intissue. For example, a delivery catheter having a dehydrated articleformed from of the present water-swellable composition can be positionedin the lumen of the catheter and introduced to the site of the openingin tissue. The dehydrated article can then be pushed from the lumen ofthe catheter into the opening and the catheter withdrawn from the site.The article expands upon being hydrated by natural fluids present at thesite. The expansion holds the article in place and serves to seal theopening.

In another embodiment, a suture is formed at least in part of thepresent water-swellable composition. For example, a conventional suture(either bioabsorbable or nonbioabsorbable; monofilament ormultifilament), may be coated with a composition in accordance with thisdisclosure and used in the same way as the conventional suture. FIG. 1depicts a suture-needle combination 10 that includes a needle 12 and anelongate thread of suture material 14 formed at least in part of acomposition in accordance with this disclosure. The suture 14 is adaptedto be pulled by a needle 12 to sew closed an opening in tissue. Thesuture can have a diameter slightly less than a diameter of the needle,there being a clearance space about the suture equal in diameter to thediameter of the needle less the diameter of the suture. Due to thepresence of coating 15 made from the present water-swellable compositionon the underlying suture 11 (in this case a monofilament), the sutureexpands upon contact with moisture that is naturally present in bodilyfluid until the suture seals the clearance space. Thus, the body'snatural moisture, in most applications, will advantageously cause thesuture or the suture coating to expand to fill the space around itcreated by the larger diameter of the needle. This eliminates the needto apply an adhesive over the sutures and thus eliminates the step ofcuring the adhesive.

In another embodiment shown in FIG. 2, coated staple 20 is shown. Asseen therein, a rigid medical staple 22 is coated with a composition inaccordance with this disclosure. Due to the presence of coating 25 madefrom the present water-swellable composition, the staple expands uponcontact with moisture that is naturally present in bodily fluid untilany openings made by the stapling procedure are filled.

In yet another embodiment, the present compositions are used to providehemostasis. It is contemplated, for example, that dried sheets of thepresent copolymers can be ground to a suitable particle size (e.g.,10-1,000 μm) and sprinkled as a dry powder onto a bleeding or otherwiseoozing wound. The particles absorb liquid, swell and rapidly stop thebleeding. It is further contemplated that the present water-swellablecopolymer compositions can be coated onto particles of suitable size andthe coated particles dehydrated. The particles may be made from anybiocompatible material that is either absorbable or non-absorbable bythe body. Non-limiting examples of suitable materials from which theparticles can be made include silica, polysaccharides (for example,crosslinked dextran such as Sephadex beads, hyaluronic acid, aliginate,carboxy methyl cellulose, ionically modified dextrans, e.g. sulfonatedor aminated dextrans, protein microspheres, such as gelatin collagen andDNA etc., and bioabsorbable polymers (such as, for example, those formedfrom one or more of glycolide, lactide, p-dioxanone, ε-caprolactone,trimethylene carbonate, and the like). The dried, coated particles arethen sprinkled as a dry powder onto a bleeding or otherwise oozingwound. Due to the coating in accordance with this disclosure, theparticles absorb liquid, swell and rapidly stop the bleeding andconcentrate or superconcentrate clotting factors creating clots. It isfurther contemplated that the present water-swellable copolymercompositions can be coated onto a sheet material (e.g., film, mesh,non-woven, foam and the like) and the coated sheet dehydrated. Thedried, coated sheet can then be applied to a bleeding wound to achievehemostasis or otherwise oozing wound to stop the oozing and assist inhealing. Due to the coating in accordance with this disclosure, thesheets absorb liquid, swell and rapidly stop the bleeding.

It should also be understood that there may be applications wherewaiting for natural body fluids to activate the dehydrated article orcoated medical device prepared in accordance with this disclosure iscontraindicated. In those applications, saline or other suitable sourceof moisture can be provided (e.g., injected) to the site at which thearticle or coated medical device has been applied to tissue. In thisway, the time required for full expansion of the article or coatedmedical device can be reduced.

EXAMPLES

Solutions of monomer containing 0.5% (w/w) HEMP and 2% (w/w) MBAA wereprepared. Monomer solutions were mixed in ratios so that the totalmonomer concentration was 20% (w/w) in water. Two monomer solutions werecombined to provide the compositions containing each monomer in amountsthat varied from 25 to 75% by weight in combination as set forth inTable A. Five milliliter samples (×3) of each composition in Table Awere irradiated using a UV flood lamp for anywhere from 1 to 5 minutes.Most compositions were cured in less than 30 seconds. Table A shows theaverage percentage weight gain for an n=3 for each composition startingfrom a dehydrated state at time zero.

TABLE A Time in Comp^(†) Water KSPA-NaA KSPA-Tris NaA-Tris AMPS-Tris 2510 873.9 432.95 202.0 370.3 25 30 2844.1 1114.2 308.7 547.7 25 60 4547.72046.9 437.2 706.2 25 90 5163.4 2326.0 1013.0 778.7 25 120 5552.6 2509.91234.0 823.1 50 10 511.2 406.9 239.9 1057.0 50 30 2794.0 1906.3 522.91543.5 50 60 5491.2 3374.1 778.2 1706.7 50 90 6179.9 3712.9 1450.51714.6 50 120 6422.15 4187.3 1925.7 1677.0 75 10 303.5 292.5 624.72677.4 75 30 778.96 2050.8 1958.3 3969.4 75 60 2926.5 4084.2 3729.13816.55 75 90 5933.8 5215.15 4537.1 3814.4 75 120 8428.9 6414.8 5146.13789.35 ^(†)percentage of the first of the two monomers listed. Forexample MEAN(KSPA-NaA) with comp = 25 refers to the 25/75 KSPA/NaAcomposition.

Samples were dried overnight in hood and then dried in vacuum oven over24 hours. Swelling studies were performed to determine water gain oneach sample. The study consisted of weighing each dried sample. Next,samples were placed into beakers and water was added in excess. After 10minutes in the water, the water was drained and the samples wereblot-dried using texwipes. The samples were re-weighed. The samples wereplaced back into the beakers, water was added. The procedure wasrepeated at various times of immersion in water (i.e., 30 min., 60 min.,90 min. and 120 minutes).

Rate of swelling information shows that the rate of swelling as well asthe amount of total swelling depends on the copolymer composition. TheAMPS-Tris compositions swelled the least of all then synthesizedcompositions, and showed a plateau in swelling at compositionscontaining more than 50% AMPS. Additionally, increasing amount of KSPAin KSPA-NaA and KSPA-Tris compositions increased the total amount ofweight gain, but it did not necessarily follow that the rate of weightgain also increased. In general, KSPA-NaA>KSPA-Tris>NaA-Tris>AMPS-Triswith respect to the total amount of weight gain.

It will be understood that various modifications may be made to theembodiments disclosed herein. Therefore, the above description shouldnot be construed as limiting, but merely as exemplifications ofpreferred embodiments. Those skilled in the art will envision othermodifications within the scope and spirit of the claims appended herein.

1-24. (canceled)
 25. A surgical staple comprising a wire adapted to bepassed into tissue and a coating on at least a portion of the wire, thecoating containing a copolymer that includes a first monomer and asecond monomer that is different from the first monomer, wherein boththe first and second monomer are selected from the group consisting of3-sulfopropyl acrylate potassium salt, sodium acrylate, N-(tris(hydroxylmethyl)methyl)acrylamide, and 2-acrylamido-2-methyl-1-propane sulfonicacid.
 26. A surgical staple as in claim 25 wherein the coating furthercomprises a therapeutically beneficial compound.
 27. A surgical stapleas in claim 25 wherein the coating further comprises a contrastingagent.
 28. A surgical staple as in claim 25 wherein the coating furthercomprises a radioactive substance.
 29. A surgical staple as in claim 25wherein the coating further comprises a dye.
 30. (canceled)